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Scientists decipher the first epigenomes of Chronic Lymphatic Leukemia

By 15 de October de 2012November 18th, 2020No Comments
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This research reveals more than one million epigenetic alterations in CLL. Source: Hospital Clínic de Barcelona.
 15.10.2012

Scientists decipher the first epigenomes of Chronic Lymphatic Leukemia

A study published today in Nature Genetics presents a new perspective in cancer research as it integrates the data from whole epigenome and genome sequencing of Chronic Lymphocytic Leukemia (CLL) patients.The research reveals more than one million epigenetic alterations, an unexpected finding indicating that cancer cells undergo extensive epigenetic reprogramming. The researchers, which include scientists from CNAG and the IRB Barcelona, based in the Barcelona Science Park– have identified the cells that give rise to the disease as well as new molecular mechanisms at play in its development, thereby improving diagnosis.


This research, directed by Iñaki Martin-Subero from Universidad de Barcelona and IDIBAPS (Barcelona, Spain), represents the first collaborative effort between two European high-impact research initiatives, such as the EU-funded Blueprint Consortium and the CLL Genome Project funded by the Spanish government. These two initiatives are set within the context of two world-wide Consortia, the International Human Epigenome Consortium and the International Cancer Genome Consortium, respectively. During the last few years, Spanish CLL Genome Consortium has published two outstanding works in Nature and Nature Genetics that characterized a mutational genome map associated with this disease.

The State Secretary for Research, Development and Innovation of the Ministry of Economy and Competitivity, Carmen Vela, presented today together with the study coordinators – Carlos López-Otín, from the University of Oviedo and Elías Campo, from the Hospital Clínic and director of the study– Iñaki Martín-Subero, from the Universidad de Barcelona and the Institute for Biomedical Research ‘August Pi i Sunyer’, the latest results of the Leukemia Genome project. Also present was the director of the Institute for Health Carlos III, Joaquín Arenas.

The State Secretary for R+D+I highlighted the “importance of this study” and affirmed that projects like this “bear witness to the quality of our science and our scientists. Any advance in this area is important. When such studies are led by Spanish scientists, in addition to being important, they are also gratifying. Spain does quality research and we are working to make sure this continues in the future.”

“In the previous research activities of Spanish CLL Genome Consortium we focused on the analysis of mutated genes involved in the development of this disease. Now, thanks to our work within the Blueprint Consortium, we have analyzed the full DNA methylome of CLL. This approach has allowed us to identify the cells of origin of this kind of leukemia and to discover new mechanisms that contribute to its development.”, says Elias Campo.

“Our previous genetic studies identified over 1000 genes mutated in the chronic lymphocytic leukemia, whereas this epigenomic analysis has allowed us to detect over a million epigenetic changes in this disease. This unexpected finding indicates that the epigenome of the cell suffers a massive shift during leukemia development”, says Dr. Lopez-Otin.

The CNAG’s contribution

Thanks to the next-generation sequencing technologies available in CNAG and the usage of the high-density microarrays, this research has decoded for the first time the complete DNA methylome of this disease and led to the unexpected discoveries and have enabled the characterization of the epigenome of leukaemia in a relatively short time. The vast amount of data generated in this project has required new methodology development and optimization, done principally by the bioinformatics groups at the CNAG, together with the research group of Dr. Martin-Subero, to unveil the epigenetic patterns for classifying patients with chronic lymphocytic leukemia in three groups with different clinical course.

According to Ivo Gut “This project highlights the importance of high resolution epigenomic analysis in disease. We gained far deeper insight into the mechanism of this disease than we had ever before and this will undoubtedly lead to great benefits for patients suffering from it.”

“Until now, most of the epigenetic studies have been concentrated on the analysis of a limited fraction of the genome, which was considered crucial for gene expression. Our results clearly show that the majority of epigenetic alterations in CLL takes place in regions of the genome that were not examined in previous studies”, explains Iñaki Martin-Subero.